How adherent do people need to be for PrEP to be effective?

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By testing participants’ blood for the presence of PrEP
drugs, researchers have attempted to estimate the number of PrEP doses they
have actually taken. They have then looked at the number of HIV infections in
people with different levels of adherence.

For example, in the iPrEX
OLE study of men who have sex with men and transgender women most
infections occurred in people taking less than two doses a week, with none
occurring in individuals taking four or more doses. The researchers calculated
the following levels of protection:

Less than two doses a week: 44% fewer infections
(credible range: -31 to 77%)

Two or three doses a week: 84% fewer infections
(credible range: 21 to 99%)

Four or more doses a week: 100% fewer infections
(credible range: 86 to 100%).

These results are relevant to HIV exposure during anal sex,
but not vaginal sex. Moreover, there are limitations to the methods used to
produce these estimates, so they should be treated with caution. In particular,
note that the ‘true’ figure for the reduction in infections associated with
four or more doses could be as low as 86%. It is not necessarily 100%.

But in practical terms, adherence is most important during
periods of exposure to HIV. If an individual knows for sure that they are not
going to have sex for a period of time, or not with anyone who could expose
them to HIV, then they may prefer to stop taking PrEP during that period.
However, it may take several days after PrEP is resumed for protective
concentrations to build up in tissues.

Factors associated with good adherence in studies include
older age, higher levels of education, perceiving oneself to be at risk of HIV
infection and having a higher level of sexual activity. While high-quality
adherence counselling is probably helpful, we know little about which
approaches are most effective.

Must PrEP be taken daily? Can intermittent dosing be effective?

Almost all PrEP studies, including PROUD, asked participants
to take PrEP every day. But one study has shown that PrEP pills can also be
very effective when people only take it before and after they have sex. This is
sometimes known as ‘intermittent’ dosing or ‘event-driven’ dosing.

In the
IPERGAY study, participants were told to take a double dose of Truvada (two pills) from 2-24 hours
before anticipated sex, and then, if sex happened, two separate doses in each
of the two days that followed.

The study was conducted in France and Canada, recruiting 400
men who have sex with men. As with the PROUD study, many had multiple sexual
partners and were at higher risk of HIV infection than many other gay men.

The rate of new HIV infections was 0.9% in the PrEP group
and 6.8% in the placebo control group, with the difference translating to an
effectiveness of 86% (credible range: 39 to 98%). Extraordinarily and
coincidentally, this was the same level of effectiveness as seen in PROUD.

The study demonstrates that good adherence to intermittent
PrEP is possible and that it can be as effective as daily PrEP. The researchers
calculated that 18 men needed to take PrEP to prevent one HIV infection in a
year.

Some participants had sex quite frequently and were
therefore taking PrEP on an almost daily basis. A minority of participants only
took a handful of pills a month, either because they were not having much sex
or because they had poor adherence.

What could be the advantages and disadvantages of intermittent dosing?

An intermittent dosing schedule could be given as an option
in future UK clinical guidelines. The approach may make adherence easier for
some people, particularly those who have a good idea when they are likely to
have sex. (For example, this is the case for some people who use dating apps.) But
personal preferences vary – other people may find the routine of daily PrEP
easier to remember.

With fewer overall doses, any missed doses will matter far
more than in a daily regimen.

As fewer pills are taken, an intermittent approach is likely
to be cheaper. For the same reason, it might reduce side-effects.

A
study in Thailand, South Africa and the United States is trying to find out
which dosing schedules are easiest to adhere to. Some participants take PrEP
daily, others follow a schedule similar to the IPERGAY study, while in a third
group participants are asked to take PrEP twice a week plus an additional dose within two hours of having sex. Full
results will be announced soon.

PrEP

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.